Artificial vessel and process for preparing the same

ABSTRACT

An artificial vessel having a compliance and a stress-strain curve approximate to those of a vital vessel, which comprises a porous part of an elastomer having pores which communicate between the inside of the vessel and the outside of the vessel and a tubular part of fibers, said tubular part being in contact with and/or bonded to at least one part of the porous part. The artificial vessel can be prevented from breakage and damage at a high blood pressure and has an excellent durability.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of application Ser. No. 840,169,filed 3/17/86, now abandoned, which is a continuation-in-part of Ser.No. 06/706,693, filed 2/28/85, now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to an artificial vessel which has astress-strain curve and a compliance approximate to those of a vitalvessel, and has pores throughout the thickness of the vessel wall, andrelates to a process for preparation of the same.

In recent days, investigation on an artificial vessel has proceeded andmany artificial vessels have been developed with the progress ofvascular surgery. At present, examples of the clinically used artificialvessels for arteries with a large diameter of not less than 6 mm are,for instance, the DeBakey artificial vessel made of woven Dacron (USCI.Co., Ltd. of U.S.A.), and Gore-Tex (Gore. Co., Ltd. U.S.A.) which ismade of an expanded potytetrafluorethylene (hereinafter refered to as"EPTFE").

Those conventional artificial vessels have pores which communicatebetween the inside of the vessel and the outside the vessel. When thevessel is grafted into a living body, the outside of the vessel iscovered with pseudointima and the pseudointima grows into thecommunicating pores to cover the inside of the vessel, i.e., the vesselis organized, which prevents the formation of thrombus or occlusion bythrombus and thus makes the artificial vessel stable in the living body.The property whereby the communicating pores serve to make theartificial vessel organize is referred to as "porosity".

The compliances of such conventional artificial vessels are verydifferent from those of vital vessels, which causes various problems dueto compliance mismatch such as anastomotic punnus hyperplasia long afterthe grafting in a living body. Particularly, the conventional artificialvessels cannot be clinically used as an artificial artery with a smalldiameter of not more than 6 mm because the compliance mismatchremarkably increases to make patency of the vessel poor. Thereforeself-veins are used for vascular reconstructive surgery of coronaryarteries or arteries below the knees.

For the above reason, in development of artificial vessels, particularlyartificial arteries with a small diameter, it is important that thecompliances of artificial vessels are matched with those of vitalvessels, in addition the artificial vessels having a porosity and theblood compatibility of artificial vessels being improved.

According to the report by Sasajima et al, J. Artif. Organs 12(1),179-182(1983), however, the compliance of the practically availableartificial vessels is much smaller than those of vital vessels, as shownin Table 1. As is clear from Table 1, the practically availableartificial vessels are very hard to comparison with vital arteries, inother words, the artificial vessel is like a rigid vessel.

                  TABLE 1                                                         ______________________________________                                        Vessel            Compliance                                                  ______________________________________                                        Thoracic aorta of dog                                                                           0.749                                                       Abdominal aorta of dog                                                                          0.491                                                       Carotid artery of dog                                                                           0.356                                                       Double Velour Dacron                                                                            0.058                                                       Woven Dacron      0.021                                                       EPTFE             0.028                                                       ______________________________________                                    

In order to solve such compliance mismatch, a process for preparing anartificial vessel of an elastomer which has a porous wall and acompliance approximate to that of a vital vessel is disclosed in U.S.Pat. No. 4,173,689. The artificial vessel prepared according to theprocess does not have porosity. Further, the artificial vessel has verysmall pores on its wall and a relatively dense structure. Although thecompliance of the artificial vessel prepared according to the processdisclosed in the U.S. Patent is surely larger than that of theconventional artificial vessel, the compliance is still smaller thanthat of a vital vessel and is not sufficient.

For preparing an artificial vessel approximate to a vital vessel, itshould be attempted to match the stress-strain curve of an artificialvessel with that of a vital vessel. The typical stress-strain curve ofone of the prior artificial vessels is curve I in FIG. 4, andstress-strain curves of vital vessels are curves III and IV in FIG. 4.As is clear from FIG. 4, when a high blood pressure beyond normal bloodpressure range is applied to those vessels, the stress-strain curve I ofthe prior artificial vessel shows different behaviour from those of thecurves III and IV of the vital vessels. Accordingly, the priorartificial vessels have possibilities of breakage and damage when anabnormal blood pressure is applied, for instance, in a surgicaloperation, and also have insufficient durability.

An object of the present invention is to provide an artificial vesselhaving a porosity, and also having a compliance and a stress-straincurve approximate to those of a vital vessel.

Another object of the invention is to provide a process for preparingsuch an artificial vessel.

These and other objects of the invention will become apparent from thedescription hereinbelow.

SUMMARY OF THE INVENTION

According to the present invention, there is provided an artificialvessel having a compliance and a stress-strain curve approximate tothose of a vital vessel, which comprises a porous part of an elastomerand a tubular part of fibers which are in contact with and/or are bondedto at least one part of the porous part.

The artificial vessel can be prepared according to a process comprisinga step of coating a mandrel with an elastomer solution containing apore-forming agent and/or an elastomer solution having a cloud point,and a step of immersing the coated mandrel into a coagulating liquid,the steps being repeated one or more times, wherein a tubular element offibers is arranged on the mandrel in at least one of the steps.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B show a schematic longitudinal sectional view and aschematic cross sectional view respectively of an embodiment accordingto the present invention;

FIGS. 2A and 2B show a schematic longitudinal sectional view and aschematic cross sectional view respectively of another embodimentaccording to the present invention;

FIGS. 3A and 3B show a schematic longitudinal sectional view and aschematic cross sectional view respectively of still another embodimentaccording to the present invention; and

FIG. 4 is a graph of stress-stain curves of a prior artificial vessel I,an artificial vessel II of the present invention and vital vessels III,IV.

DETAILED DESCRIPTION

The elastomer used in the present invention is a thermoplastic elastomerwhich has fine blood compatibility. Namely the elastomer does notrelease any low molecular compound which causes acute poisoning,inflammation hemolysis, fever, and the like, and does not subject theblood to serious damage. The thermoplastic elastomer also has a superiorantithrombogenicity. Examples of the elastomers are, for instance,polystyrene elastomers, polyurethane elastomers polyolefin elastomers,polyester elastomers, elastomers which are blended with other polymersto the extent of retaining the property of an elastomer, and a mixturethereof. Among them, a hydrophobic elastomer having a critical sufacetension of less than 35 dye/cm, preferably less than 30 dyn/cm issuitably employed.

When the hydrophobic property of the elastomer becomes larger, theartificial vessel has advantages in that affinity of the graftedartificial vessel to soft tissues surrounding the vessel can be reduced,that interaction between the artiticial vessel and blood components canalso be reduced and that water resistance of the artificial vesselbecomes large. It should be noted that, when the affinity is large,there is a tendency that soft tissues are formed thickly around thegrafted artificial vessel and are tightly fixed to the vessel. Thisresults in the artificial vessel becoming narrower and deformed.

From viewpoints of strength, elongation, durability andantithrombogenicity, polyether type segmented polyurethane elastomersare more preferable. A segmented polyurethane which contains fluorineatom in a hard segment or a soft segment, and a segmented polyurethanedisclosed in Japanese Unexamined Patent Publication (KOKAI) No.211358/1982, which contains dimethylsiloxane in its main chain, arestill more preferable. Particularly preferable is a segmentedpolyurethane which contains, in a part of a soft segment,dimethylsiloxane having the formula: ##STR1## wherein R₁, R₂, R₃, R₄, R₅and R₆ are an alkylene group having at least 1 cabon atom, preferably analkylene group having 2 to 6 carbon atoms such as ethylene, propylene,butylene or hexamethylene; a and g are 0 or an integer of 1 to 30; b, c,e and f are 0 or 1; d is an integer of not less than 2.

In the artificial vessel of the present invention, the wall of thevessel comprises the porous part of the elastomer and the tubular partof fibers.

According to the present invention, the porous part exists over theentire thickness of the vessel wall from the inner surface to the outersurface. The pores are communicated with each other in at least one partthereof, and open to the exterior on the inner surface and the outersurface of the vessel. Therefore, the artificial vessel has porosity.The pores are defined by continuous partitions of the elastomer. It ispreferable, for obtaining the artificial vessel having a compliance anda stess-strain curve approximate to a vital vessel, that the partitionhas a number of small pores and holes with a maximum diameter of lessthan 1 μm, which makes the partition bulky. Such a bulk structure cannotbe formed by drying a coated elastomer solution or by cooling a moltenelastomer, but can be readily formed according to the process of thepresent invention. The most preferable porous structure is a networkstructure where substantially uniform pores are formed over the entirethickness of the vessel wall from the inner surface to the outersurface.

The porous parts in the inner surface area and the outer surface areaare sometimes relatively dense in comparison with the predominant partbetween the two areas. In such a case, the pore does not have acompletely even diameter throughout its length. Unless the unevenness ofdiameter has a bad influence on the porosity, however, the pore havingsuch an uneven diameter is regarded as a uniform pore. The maximumdiameter of the pore is preferably 1 to 100 μm, more preferably 3 to 75μm. When the maximum diameter is larger than 100 μm, the strength of thevessel tends to be weak and its porosity tends to be too big. When themaximum diameter is smaller than 1 μm, the porosity of the vessel tendsto be small and the compliance of the vessel also tends to be too small.

There are openings formed by the pores of the porous structure in theinner and outer surfaces. Although the shape of the small pores are notparticularly limited, it is preferable that the opening in the innersurface is a circle or oval. The maximum diameter of the opening is 1 to100 μm, more preferably 5 to 50 μm, most preferably 10 to 30 μm. Whenthe maximum diameter is larger than 100 μm, the flow of blood isdisturbed and the antithrombogenicity is reduced. When the maximumdiameter is smaller than 1 μm, it takes a long time to organize theartificial vessel.

The compliance of the porous part is approximate to that of a vitalvessel or may be larger than that of a vital vessel. When the complianceof the porous part is larger than that of a vital vessel, the totalcompliance of the artificial vessel can be adjusted by combination ofthe tubular element of fibers. The porous part of the vessel having sucha compliance can be prepared by controlling the percentage of the poresin the porous part, strength of the partition, strength of theelastomer, and the like.

The fiber which forms the tubular part is a fine and long fiber having alength more than 100 times larger than the diameter, which is usuallyemployed for producing a yarn, a net yarn, a rope, a woven fabric, aknitting fabric, a braid, a nonwoven fabric, or the like. The fiber maybe made of an organic material or of an inorganic material, as long asthe fiber does not have any bad influence on a living body, degradationof the fiber in a living body can be negligible, and the fiber is stablein sterilizing treatment, and also the fibers can form a tubularelement. From viewpoints of processability, commercial availability,pliability and uniformity, there are preferably employed a regeneratedman-made fiber, a semi-synthetic fiber and a synthetic fiber. Examplesof the fiber are, for instance, cellulose type fibers, protein typefibers, polyurethane type fibers, polyethylene type fibers, polystyrenetype fibers, polyvinylchloride type fibers, polyvinylidene chloride typefibers, polyfluoroethylene type fibers, polyacrylic type fibers,polyvinyl alcohol type fibers, and the like. Among them, a fiber havinga stretching property is more preferably employed. Examples of such astretch fiber are, for instance, fiber having a self-stretching propertysuch as rubber type fibers, polyurethane type fibers or polyesterelastic type fibers; stretch bulked fibers such as Woolie nylon orWoolie tetron; covered yarns prepared by winding a spun yarn or filamenton an elongated rubber filament or a Spandex filament; and the like.

The tubular element used in the present invention comprises theabove-mentioned fiber; a yarn spun from at least one of theabove-mentioned fibers; a multifilament of at least one of theabove-mentioned fibers; a woven fabric, a knitting, a braid, a nonwovenfabric or a fabric combined thereof, which are produced from the abovefiber, yarn or multifiber; a polyurethane foam of sponge like structure;and the like.

The tubular part may be formed by using a pre-formed tubular element ofthe fibers or by combining the fibers with the porous part of theelastomer so as to form the tubular structure at the finishing. Fromviewpoints of processability, workability and establishment of thestress-strain curve approximate to a vital vessel, there is preferablyemployed a tubular element of the knitting fabric, more preferably atubular element of a knitting fabric of stretch yarns.

The tubular element used in the present invention is not particularlylimited to the above-mentioned materials insofar as that the aritificialvessel prepared by combining the tubular element with the porous part ofthe elastomer has a compliance and a stress-strain curve approximate tothose of a vital vessel. Such properties of the tubular part can beachieved by controlling the number of the connecting or contactingpoints of the fibers or yarns, by adjusting the tightness of theconnecting point of the fibers or yarns, or by using a stretch fiber.

According to the present invention, the arrangement of the tubular partis not particularly limited insofar as that the tubular part iscontacted with and/or bonded to at least one portion of the porous part.FIG. 1 shows an embodiment of the arrangement according to the presentinvention. In this embodiment, the tubular part 2 is incorporated at amiddle portion of the porous part 1. In such a case there are advantagesthat frying of the fiber can be prevented and that a superiorantithrombogenicity of the vessel can be maintained at a contact surfacewith blood. The tubular part 2 may be arranged at the outer side of theporous part 1, as shown in FIG. 2, so that the outer area of the tubularpart 2 is exposed to the exterior of the porous part 1. Further, asshown in FIG. 3, the tubular part 2 may be arranged at the inner side ofthe porous part 1 so that the inner area of the tubular part 2 isexposed to the interior of the porous part 1.

The wording "the tubular part is in contact with and/or is bonded to theporous part" used herein means that there is a dynamic interactionbetween the tubular part and the porous part so that both the tubularpart and the porous part show almost the same strain against a stresssuch as a blood pressure or a pressure applied from outside.

Preferable compliance for an artificial vessel cannot absolutely definedbecause the compliance is different depending on the diameter of thevessel, the portion to be grafted, the kind of the vessel, and the like.According to the present invention, the artificial vessel having acompliance approximate to that of a vital vessel can be produced. Ingeneral, since a compliance of a vital vessel which is used for vascularreconstruction surgery is about 0.1 to 0.8, the compliance is preferablywithin the range as mentioned above. According to the present inventionthe artificial vessel having any compliance within the range of 0.1 to0.8 can be produced. The artificial vessel with a compliance of 0.1 to0.8 can be preferably used as an artery with a proper diameter.Particularly the artificial vessel having an inside diameter of 1 to 6mm with a compliance of 0.1 to 0.5 can be preferably used as an arterywith a small diameter.

The "compliance approximate to that of a vital vessel" is referred toherein in the sense that the artificial vessel has the complianceapproximate to that of a vital vessel having the inner diameter and thethickness of the vessel wall both approximate to those of the artificialvessel. Therefore, the artificial vessel having the inner diameter offrom 2 to 6 mm, the thickness of the vessel wall of from 0.2 to 1.5 mmand the compliance of from 0.2 to 0.5 can preferably be used as arterieswith a small diameter and the artificial vessel having the innerdiameter of from 2 to 6 mm, the thickness of the vessel wall of from 0.4to 1.3 mm and the compliance of from 0.3 to 0.5 can more preferably beused as arteries with a small diameter.

The "compliance" as used herein is defined by the equation (1): ##EQU1##wherein C is compliance, Vo is volume of a measured vessel at the innerpressure of 50 mmHg, ΔP is the pressure difference (100 mmHg) in theinner pressure of 50 mmHg to 150 mmHg, ΔV is the increase in the volumeof the vessel when the inner pressure rises from 50 mmHg to 150 mmHg. Inpractical measurement, a vessel is inserted into a closed circuit, andthe volume of an injected liquid and the pressure variation in thecircuit are measured by means of a microanalysis pump and a pressuregauge. From the results, the compliance can be calculated according tothe equation (1).

The stress-strain curves of artificial vessels and vital vessels areshown in FIG. 4. The stress-strain curves are the curves obtained bymeasuring in the axial direction with a tension testing machine which isusually employed in the polymer material field, for instance, AutographIS2000 commercially available from Shimadzu Corporation.

In FIG. 4, the curve I, II, III and IV show stress-strain curves of aprior artificial vessel consisting of a porous wall made of anelastomer, the artificial vessel of the present invention, a thoracicaorta of a vital vessel and a carotid artery of a vital vessel,respectively. It is difficult to quantitatively determine astress-strain curve of a vital vessel because the curve varies dependingon the kinds of vessel such as an artery or a vein, diameter, age,individual difference, and the like. In general, however, thestress-strain curve of the vital vessels III and IV behave in common soas to show a small elastic modulus within a normal blood pressure rangeand to show a drastic increase of the elastic modulus when a stressbeyond the normal blood pressure range is applied, as shown in FIG. 4.As is clear from FIG. 4, the artificial vessel of the present inventionshows the stress-strain curve II approximate to those of the vitalvessels III and IV.

The wording "a stress-strain curve approximate to that of a vitalvessel" used herein means a stress-strain curve approximate to thecurves III or IV.

Namely, a preferable artificial vessel of the present invention has astrain of 0.1 to 0.8, preferably 0.2 to 0.6 at a stress of 0.01 kg/mm²,at which point the vessel has an elastic modulus of not more than 0.1kg/mm², preferably 0.07 kg/mm². Also, at a stress of 0.05 kg/mm², thevessel has a strain which is larger than the strain at the stress of0.01 kg/mm² and is of 0.4 to 1.2, preferably 0.5 to 1.0, at which pointthe vessel has an elastic modulus of not less than 0.12 kg/mm²,preferably 0.2 to 10 kg/mm². Further, at a stress of 0.12 kg/mm², thevessel has a strain which is larger than the strain at the stress of0.05 kg/mm² and is of 0.5 to 1.5, preferably 0.55 to 1.2, at which pointthe vessel has an elastic modulus which is larger than the elasticmodulus at the stress of 0.05 kg/mm² and is of not less than 0.2 kg/mm²,preferably not less than 0.3 kg/mm².

As a test piece for measurement of the stress-strain curve, there ispreferably employed an artificial vessel as it is, because a stripprepared by cutting a vessel along its length often shows a differentstress-strain curve due to change of the strength of the tubular part ofthe fibers. A stress-strain curve in the circumferential direction isnot particularly limited, but is preferably approximate to that in theaxial direction.

The "stress" is calculated by dividing the load applied at the tensiontest by a section area of the test piece (section area of a vessel wall)before the test. The "strain" is calculated by dividing the elongationat the test by the length of the test piece before applying the load.The "elastic modulus" is the inclination of a tangent at any point on astress-strain curve, i.e. tangent elastic modulus.

Since the region where a small stress is applied corresponds to theregion of normal blood pressure where a compliance is measured, if acompliance of an artificial vesel is approximate to that of a vitalvessel, the stress-strain curve of the artificial vessl is approximateto that of a vital vessel. In the region where a large stress isapplied, the stress-strain curve of the artificial vessel is approximateto that of a vital vessel to such an extent that the artificial vesselretains durability for a long time and has strength enough to preventthe vessel from breakage and damage when an abnormal blood pressure isapplied to the vessel, for instance, in surgical operation.

In the artificial vessel of the present invention, the compliance andthe strain measured under normal blood pressure mainly depend on thestrength of the porous part made of the elastomer. The strain under alarge stress beyond the normal blood pressure range depends on thestrength of the tubular part made of the fibers. Accordingly, thecompliance and the stress-strain curve of the artificial vessel can bemade approximate to those of a vital vessel by combination of the abovestrengths.

According to the present invention, since the artificial vessel has thestress-strain curve approximate to that of a vital vessel, breakage anddamage can be prevented when a drastic increase of blood pressurehappens in surgical operation and excellent durability can be retainedfor a long time after grafting.

The inner surface area of the artificial vessel, that is, a surface areacontacting with blood has a superior blood compatibility because theblood compatibility of the elastomer is excellent. In order to improveantithrombogenicity of the vessel in the first stage of grafting in aliving body, the inside wall may be coated with albumin, gelatin,chondroitin sulfuric acid, a heparinized material, and the like.

The preparation of the artificial vessel of the present invention isexplained hereinbelow.

The artificial vessel of the invention can be prepared in accordancewith a process comprising a step for coating a mandrel with an elastomersolution containing a pore-forming agent and/or an elastomer solutionhaving a cloud point and a step for immersing the coated mandrel into acoagulating liquid, the steps being repeated one or more times, whereina tubular element of fibers is arranged on the mandrel in at least oneof the steps.

The elastomer solution which can be used in the present invention isroughly classified into (1) an elastomer solution containing apore-forming agent, (2) an elastomer solution having a cloud point and(3) an elastomer solution containing a pore-forming agent and having acloud point.

The elastomer solution (1) essentially comprises a pore-forming agent,the elastomer and a solvent which can dissolve the elastomer(hereinafter referred to as "good solvent") in which the pore-formingagent are uniformly dispersed. When the elastomer solution is dippedinto the coagulating liquid, the elastomer is deposited due toreplacement of the good solvent with the coagulating liquid. Thepore-forming agent in the deposited elastomer is dissolved and removedto give the artificial vessel of the present invention. If necessary forcontrolling the coagulation rate of the elastomer solution and thedensity or shape of the porous structure, a solvent which cannotdissolve the elastomer but can be miscible with the good solvent(hereinafter referred to as "poor solvent") may be added.

The elastomer solution (2) essentially comprises the elastomer, the goodsolvent and the poor solvent. The poor solvent is employed in such anamount that the solution has a cloud point. The "cloud point" means atemperature at which a dissolved polymer in a solution is deposited in aform of colloid, in other word, a temperature at which phase changeoccurs. When the elastomer solution (2) is handled at a temperaturebelow the cloud point, it is difficult to form a uniform coating of theelastomer solution, and thus a proper porous structure cannot beobtained. Therefore, it is preferable to coat the mandrel with theelastomer solution at a temperature above the cloud point, and then toimmerse the coated elastomer solution into the coagulating liquid of atemperature below the cloud point. According to the procedure, theporous part can be formed by changing the phase of the elastomersolution in the coating layer and depositing the elastomer in thecoagulating liquid in the above order or at the same time.

The elastomer solution (3) essentially comprises the elastomer, thepore-forming agent, the good solvent and the poor solvent, the amount ofthe poor solvent being such an amount that the solution has a cloudpoint. From the elastomer solution (3), the porous part can be formed inthe same procedure as in the elastomer solution (2).

The concentration of the elastomer in the elastomer solution variesdepending on the kinds of elastomer or compositions of the solution, andis not particulary limited. Preferable concentration is 5 to 35% (% byweight, hereinafter the same), more preferably 10 to 30%, mostpreferably 12.5 to 25%. When the concentration is less than 5%, it isdifficult to form a uniform porous structure. On the other hand, whenthe concentration is more than 35%, the elastomer solution tends to behardly applied because of high viscosity of the solution.

The pore-forming agent is not particularly restricted insofar as it isinsoluble in the good solvent and can be removed during or after thepreparation of the artificial vessel. Since the artificial vessel isgrafted in a living body, it is desired that the pore-forming agent ispharmacologically acceptable. Examples of the pore-forming agents are,for instance, an inorganic salt such as a common salt or calciumcarbonate, a water soluble saccharose such as glucose or starch, aprotein, and the like. The inorganic salt such as a common salt and thewater-soluble saccharose should be treated carefully because the finelydivided salt and saccharose may form a second agglomeration by moisturein the air due to their hygroscopy. From such a point of view, theprotein is preferable, because even when the protein is finely divided,the fine particles do not form the second agglomeration by moisture inthe air, and thus can stably produce the pores.

In addition since the protein can be easily dissolved in an alkalisolution, an acid solution and a solution of an enzyme, the removal ofthe protein can be easily carried out. Examples of the proteins are, forinstance, casein, collagen, gelatin, albumin, and the like. The particlesize of the pore-forming agent is preferably not more than 74 μm, morepreferably not more than 50 μm, most preferably not more than 30 μm. The"particle size" used herein means the length of a side of a sieve to beused. A pore-forming agent having a particle size larger than 74 μmtends to produce pores which are too large.

The amount of the pore-forming agent (percentage of volume of thepore-forming agent to volume of the elastomer in the elastomer solution)varies depending on the required porosity and the particle size of thepore-forming agent and the composition of the elastomer solution,particularly existence of the cloud point. The preferable amount is 20to 500%, more preferably 50 to 350%, most preferably 100 to 300%. Whenthe amount of the pore-forming agent is more than 500%, the porositytends to be too large, and the viscosity of the elastomer solution tendsto be too high. On the other hand, when the amount is less than 20%, theporosity tends to be poor.

Examples of the good solvent used in the present invention are, forinstance, N,N-dimethylacetamide, N,N-dimethylformamide,N-methyl-2-pyrrolidone, dioxiane, tetrahydrofuran, a mixture thereof,and the like. However, the good solvent should be selected according tothe kind of the elastomer used.

As the poor solvent, there can be employed any solvent which cannotdissolve the elastomer, but can be miscible with the good solvent.Examples of the poor solvents are, for instance, water, a lower alcohol,ethylene glycol, propylene glycol, 1,4-butane diol, glycerine, a mixturethereof, and the like.

The coagulating liquid may be substantially the same as the poorsolvent. Examples of the coagulating liquid are, for instance, water, alower alcohol, ethylene glycol, propylene glycol, 1,4-butane diol,glycerin, a mixture thereof, and the like. Preferable coagulating liquidis water, ethylene glycol, propylene glycol, and a poor solvent mainlycomprising one of them. Most preferable coagulating liquid is a mixedsolvent comprising 99 to 50% by volume of the poor solvent and 1 to 50%by volume of the good solvent. When using a mixed solvent, the excellentporosity can be easily obtained because the coagulation rate of theelastomer solution in the coagulating liquid becomes low due to the goodsolvent mixed with the poor solvent.

The mandrel used in the present invention is not particularly limitedinsofar as the mandrel is not dissolved in the elastomer solution.Preferable mandrel is a rod having a smooth surface such as a glass rod,a teflon rod or a stainless steel rod. When using dies having shapesinstead of the rod, various medical articles other than the abovetubular article can be obtained. For instance, if a plate is used as thedie, there can be provided a film-like article which can be utilized asan artificial skin.

As typical procedure for arranging the tubular element of the fibers onor over the mandrel, there can be employed a procedure where the mandrelis covered with the tubular element, or a procedure where the fibers ora strip of the fibers are wound on the mandrel. The tubular element maybe arranged directly on the mandrel or may be arranged on the mandrelvia the deposited elastomer layer. It is preferable that the tubularelement is arranged on the mandrel via the deposited elastomer layer andthen the step for coating of the elastomer solution and the step fordeposition of the elastomer are repeated one or more times.

The artificial vessel of the present invention has the followingexcellent properties.

(1) The artificial vessel has a porosity useful for organization of thevessel.

(2) The artificial vessel has a compliance approximate to that of avital vessel.

(3) The artificial vessel has a stress-strain curve approximate to thatof a vital vessel.

In addition, the artificial vessel of the present invention has thefollowing usable properties, since the wall of the artificial vesselsubstantially comprises the porous part of the continuous elastomerand/or is bonded to the porous part.

(4) A surgical needle easily penetrates the artificial vessel, and thusthe vessel is easily sutured.

(5) A bore formed by a needle can close by itself.

(6) Kinks are not formed in the practical use where blood pressure isapplied.

The artificial vessel having the above-mentioned characteristicproperties is excellent in patency when grafted in a living body anddoes not cause a problem such as anastomotic punnus hyperplasia. Alsosince breakage and damage of the vessel seldom happen even if bloodpressure drastically increases in surgical operation, the artificialvessel can maintain durability for a long time. Further, workability ofthe artificial vessel in vascular reconstructive surgery is alsoexcellent.

Therefore, the artificial vessel of the present invention can be used asan artificial vessel, an artificial vessel for by-pass, a material forpatch in vascular reconstruction surgery of vital vessel, moreover, ablood access. In addition, the artificial vessel with a compliance of0.1 to 0.8 can be used as an artificial artery. Since the artificialvessel of the present invention has the compliance and the stress-straincurve approximate to those of a vital vessel, the artificial vessel canbe used as an artificial artery with a small diameter of about 1 to 6 mmwhose compliance is 0.1 to 0.5, which artificial vessel has not hithertobeen available in clinical use. Such artificial vessel is preferablyused as an artificial vessel in vascular reconstruction surgery ofarteries below the knees and as an artificial vessel for a by-passbetween the aorta and coronary. In addition, the artificial vessel ofthe present invention can also be used as an artificial tube for a softvital tube such as an ureter.

The present invention is more particularly described and explained bymeans of the following Examples. It is to be understood that the presentinvention is not limited to the Examples and various changes andmodifications may be made in the invention without departing from thespirit and scope thereof.

EXAMPLE 1

After synthesizing a pre-polymer with 27.35 parts (part by weight,hereinafter the same) of 4,4'-diphenylmethane diisocyanate and 54.7parts of polyoxytetramethylene glycol (average molecular weight: 2000),the pre-polymer chain was extended with 4.75 part of ethylene glycol and13.2 parts of polydimethylsiloxane having polyethylene glycol at theboth ends (average molecular weight of polyethylene glycol: 681, averagemolecular weight of polydimethylsiloxane: 1040) to give segmentedpolyurethane containing polydimethylsiloxane in the main chain.

The polyurethane thus obtained had a tensile strength of 350 kg/cm², anelongation of 670% and a critical surface tension calculated from Zismanplot of 28 dyn/cm.

In a mixed solvent of 50 ml of dioxane and 30 ml ofN,N-dimethylacetamide was dispersed 22.5 g of casein having a particlesize of not more than 30 μm with a homogenizer, and 15 g of thesegmented polyurethane was added to the dispersion, and then wasdissolved with agitation. A glass rod having a diameter of 3 mm wascoated with the solution by immersing the glass rod into the solutionand taking out of the solution. Subsequently, the coated glass rod wasimmersed into ethylene glycol to deposit the elastomer on the rod.

A tubular element having an inner diameter of about 3 mm was prepared byknitting a covered yarn with a ribbon knitting machine having a 12needle head. The covered yarn was formed by winding a nylon fiber of 70deniers on a Spandex of 20 deniers. After the glass rod coated with theelastomer was covered with the tubular element, the glass rod wasimmersed into the elastomer solution. The coated glass rod was thenimmersed into the coagulating liquid to deposit the elastomer in and onthe tubular element, followed by removing the coagulating liquid fromthe surface. The coating procedure and the coagulation procedure wererepeated once. After washing the deposited elastomer with water, thetubular article was taken off the glass rod. The casein particles wereremoved from the tubular article by dissolving in an aqueous sodiumhydroxide solution of pH 13.5, and then the tubular article wassufficiently washed with water to give the artificial vessel of thepresent invention.

The artificial vessel obtained had an inner diameter of about 3 mm andan outer diameter of about 4.5 mm. As a result to of observation with ascanning type electron microscope, there were circular and oval openingsof about 20 to 30 μm in diameter on the inner surface of the vessel, andthere were circular and amorphous openings of about 1 to 10 μm indiameter on the outer surface. The tubular element was incorporated inthe center part of the vessel wall and the other part was made of theelastomer of network structure which was constructed by the partitionsof the elastomer and the pores, the maximum diameter of the pores beingabout 5 to 70 μm. The partitions had very small pores and holes with amaximum diameter of less than 1 μm which were formed by replacementbetween the good solvent and the coagulating liquid and thus had a bulkystructure.

The porosity of the artificial vessel was confirmed by passing waterthrough the vessel under a pressure of 120 mmHg (gauge). A volume ofwater which penetrating from inside to outside was about 50 ml/min per 1cm² of the inner surface.

After pre-clotting blood of bovine origin in the vessel and cutting thepre-clotted vessel to 8 cm, the artificial vessel was inserted into aclosed circuit. The ACD blood of bovine origin was fed into the closedcircuit by a quantitative pump which fed 0.05 ml per stroke, and thechange of the inner pressure was measured. The compliance calculatedaccording to the equation (1) on the basis of the numbers of strokes andthe change of the inner pressure was 0.30.

By using Shimadzu Autograph IS2000, a stress-strain curve was measured.The stress-strain curve of the artificial vessel was the curve II shownin FIG. 4 which is approximate to the curves III and IV of vitalvessels.

The artificial vessel of about 7 cm in length was grafted to a femoralartery of an adult mongrel dog. The grafted vessel showed a patency formore than two months.

The artificial vessel did not fray when cut at any point, and wasexcellent in suturing property. In addition, the bores of the surgicalneedle closed by themselves when the needle was removed. Further, thevessel tended not to form kinks under an inner pressure of 50 to 150mmHg.

As a result of the above data, it is clear that the artificial vesselhas excellent properties as an artificial vessel for an artery with asmall diameter.

EXAMPLE 2

To a mixed solvent of 45 ml of propylene glycol, 57.8 ml of dioxane and24.8 ml of N,N-dimethylacetamide was added 22.5 g of casein having aparticle size of not more than 30 μm, and then was dispersed with ahomogenizer. The polyurethane prepared in Example 1 was added to thedispersion in an amount of 22.5 g and was dissolved with heating at 80°C. The resulting elastomer solution had a cloud point of about 45° C. Aglass lod having a diameter of 3 mm was immersed in the solution of 80°C. to be coated uniformly with the elastomer solution. The coated glassrod was immersed into water of 18° C. to deposit the elastomer on therod.

A tubular element having an inner diameter of about 3 mm was prepared byvery roughly knitting a twist yarn of 48 Woolie teflon fibers of 2deniers with a ribbon knitting machine having a 12 needle head. Afterthe glass rod coated with the elastomer was covered with the tubularelement, the glass rod was immersed into the elastomer solution, andthen was immersed into water. After washing with water, the tubulararticle thus obtained was taken off the rod. The casein particles wereremoved from the tubular article by dissolving in an aqueous sodiumhydroxide solution of pH 13.5, and then the article was sufficientlywashed with water to give the artificial vessel of the present invention(inner diameter: about 3 mm, outer diameter: about 4.5 mm). In theobservation of the inner surface, outer surface and section of thevessel with a scanning type electron microscope, there were ovalopenings of about 15 to 20 μm in diameter on the inner surface and therewere amorphous openings of about 5 μm in diameter on the outer surface.The tubular element was incorporated in the center of the vessel walland the other part was made of the elastomer of uniform networkstructure. The maximum diameter of the pores observed in section of thevessel wall was about 4 to 50 μm. The partitions which form a networkstructure had very small pores and holes with a maximum diameter of lessthan 1 μm which were formed by replacement between the good solvent andthe coagulating liquid and thus had a bulky structure.

The penetration volume of water and the compliance measured in the samemanner as in Example 1 were about 110 ml and 0.25, respectively.According to the stress-strain curve measured in the same manner as inExample 1, the relationship among the stress, the strain and the elasticmodulus of the vessel was as follows:

    ______________________________________                                        Stress                Elastic modulus                                         (kg/mm.sup.2) Strain  (kg/mm.sup.2)                                           ______________________________________                                        0.01          0.35    0.06                                                    0.05          0.65    0.3                                                     0.12          0.75    1.0                                                     ______________________________________                                    

EXAMPLE 3

15 g Of the polyurethane prepared in Example 1 was dissolved at 70° C.with agitation in a mixed solvent of 55 ml of N,N-dimethylacetamide and30 ml of propylene glycol. The elastomer solution had a cloud point ofabout 40° C.

A tubular element of about 3 mm in inner diameter was prepared in thesame manner as in Example 1 except that a covered yarn formed by windinga Dacron fiber of 30 deniers on a Spandex of 20 deniers was used. Aftercovering a glass rod of 3 mm in diameter with the tubular element, therod was immersed into the elastomer solution to be uniformly coated withthe solution, and then was taken out of the solution. After allowing therod to stand rod in air until the coating layer whitened, the glass rodwas immersed into water of 15° C. to replace the mixed solvent by water.The procedures were repeated again, and then the elastomer wassufficiently washed with water. The artificial vessel was obtained bytaking off the glass rod. The artificial vessel of the present inventionhad an inner diameter of about 3 mm and an outer diameter of about 4.5mm.

In the observation of the inner surface, outer surface and section ofthe vessel with a scanning type electron microscope, on the innersurface there were oval openings of about 10 μm in maximum diameterwhich were uniformly distributed, and the fibers of the tubular elementwere partially exposed. On the outer surface, there were openings of asmaller diameter than the inner surface. The vessel wall was constructedby the tubular part of the fibers and the porous part made of thecontinuous elastomer partitions which define the pores. The pores hadthe maximum diameter of from about 8 to about 60 μm. The partitionswhich form pores had very small pores and holes with a maximum diameterof less than 1 μm which were formed by replacement between the goodsolvent and the coagulating liquid and thus had a bulky structure.

The penetration volume of water and the compliance measured in the samemanner as in Example 1 were about 20 ml and 0.35, respectively.According to the stress-strain curve measured in the same manner as inExample 1, the relationship among the stress, the strain and the elasticmodulus of the vessel was as follows:

    ______________________________________                                        Stress                Elastic modulus                                         (kg/mm.sup.2) Strain  (kg/mm.sup.2)                                           ______________________________________                                        0.01          0.45    0.045                                                   0.05          0.8     0.21                                                    0.12          1.0     0.5                                                     ______________________________________                                    

What is claimed is:
 1. An artificial vessel consisting essentially offirst and second groups of concentric layers, said first groupconsisting essentially of porous fibrous material and comprising atleast one concentric layer, said second group consisting essentially ofporous segmented polyurethane elastomer and comprising at least oneconcentric layer, wherein the innermost layer of the artificial vesselis a layer of said porous segmented polyurethane elastomer, and whereinsaid groups have pores which communicate the inner surface of the vesselto the outer surface of the vessel, said vessel having a compliance anda stress-strain curve approximate to the compliance and the stressstrain curve of a vital vessel.
 2. The artificial vessel of claim 1,wherein the compliance is 0.1 to 0.8.
 3. The artificial vessel of claim1, wherein the strain is 0.1 to 0.8 at a stress of 0.01 kg/mm², thestrain is 0.4 to 1.2 at a stress of 0.05 kg/mm² and the strain is 0.5 to1.5 at a stress of 0.12 kg/mm².
 4. The artificial vessel of claim 1,wherein the segmented polyurethane elastomer contains fluorine.
 5. Theartificial vessel of claim 1, wherein the segmented polyurethaneelastomer contains a dimethylsiloxane in its main chain.
 6. Theartificial vessel of claim 1, wherein said fibrous layer is formed by aknit fabric.
 7. The artificial vessel of claim 1, wherein said fibrouslayer is formed by a knit fabric of stretch yarns.
 8. An artificialvessel consisting essentially of first and second groups of concentriclayers, said first group consisting essentially of porous fibrousmaterial and comprising at least one concentric layer, said second groupconsisting essentially of porous segmented polyurethane elastomer andcomprising at least one concentric layer, wherein the innermost layer ofthe artificial vessel is a layer of said porous segmented polyurethaneelastomer, and wherein said groups have pores which communicate theinner surface of the vessel to the outer surface of the vessel, saidvessel having a compliance of 0.1 to 0.8, and a stress-strain curve inwhich the strain is 0.1 to 0.8 at a stress of 0.01 kg/mm², the strain is0.4 to 1.2 at a stress of 0.05 kg/mm² and the strain is 0.5 to 1.5 at astress of 0.12 kg/mm².
 9. The artificial vessel of claim 8, wherein saidfibrous layer is formed by a knit fabric.
 10. The artificial vessel ofclaim 8, wherein said fibrous layer is formed by a knit fabric ofstretch yarns.